In clinical examinations such as serum biochemical examination, a blood coagulation accelerator is used when serum is to be collected from blood in a shorter time, and an enzyme is used as the blood coagulation accelerator. The enzyme used as the blood coagulation accelerator is an enzyme capable of hydrolyzing in a peptide chain a bond between arginine and an arbitrary amino acid residue and/or a bond between lysine and an arbitrary amino acid residue, and thrombin can be mentioned as a typical enzyme. Thrombin has higher blood coagulation activity than that of an inorganic blood coagulation accelerator typified by silica and the like, thus enabling rapid coagulation of blood to give serum in a very short time.
However, thrombin is an unstable enzyme which is hardly stably stored and hardly exhibits a high blood coagulation performance stably over a long period of time. Although lyophilization is conventionally used as a method of stably storing thrombin, this enzyme should be stored in an aluminum package, a glass container or the like and always kept in a suitable storage form to attain stability over a long period of time, and is hardly stably stored when stored particularly in a moisture-permeable container.
In a method of stably storing thrombin in an aqueous solution, for example, an aqueous liquid thrombin composition containing, as a stabilizer, a sugar and an amino acid is disclosed (See Patent document 1). This method is effective in short-term storage at a low temperature, but cannot be applied to a blood coagulation accelerator and a container for blood examination wherein long-term storage stability is required particularly under severe conditions at ordinary or higher temperatures.
As a technique for stabilizing a dry preparation of thrombin, for example, a dry preparation comprising sugars, a basic amino acid and an organic acid salt is disclosed (See Patent document 2).
This dry preparation is effective in low-temperature and short-term storage, but cannot be applied to a blood coagulation accelerator and a container for blood examination wherein long-term storage stability is required particularly under severe conditions at ordinary or higher temperatures. This dry preparation is liable to the influence of humidity and is thus problematic in stability, particularly when stored in a moisture-permeable container.
Patent document 1: JP-A 64-40433
Patent document 2: JP-A 2-53732